Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Graft-Versus-Host Disease

Clinical characteristics of chronic graft-versus-host disease following umbilical cord blood transplantation for adults

Bone Marrow Transplantation volume 41, pages 729–736 (2008)Cite this article

Abstract

Chronic GVHD is a significant complication following allogeneic hematopoietic stem cell transplantation; however, the clinical characteristics of chronic GVHD following cord blood transplantation (CBT) in adults have not been well described. Between March 2001 and November 2005, a total of 77 patients underwent CBT at eight transplantation centers of the Nagoya Blood and Marrow Transplantation Group. Of 77 patients, 29 survived without graft failure or progression of underlying diseases for at least 100 days after transplantation. The median age of the 29 patients was 42 years (range, 18–67 years). Seven patients developed chronic GVHD (extensive, n=4; limited, n=3) disease. The cumulative incidence of chronic GVHD 1 year after day 100 was 24% (95% confidence interval (CI), 11–41%), and the organs involved were the skin (n=6), oral cavity (n=4), liver (n=1) and gastrointestinal tract (n=1). In three patients, chronic GVHD was resolved with supportive care. The remaining four were successfully treated with additional immunosuppressive therapy. Event-free survival rates of the 29 patients with and without chronic GVHD 3 years after day 100 were 83 (95% CI, 27–97%) and 36% (95% CI, 17–56%), respectively (P=0.047). These results suggest that chronic GVHD following CBT is mild and has a graft-versus-malignancy effect.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Przepiorka D, Anderlini P, Saliba R, Cleary K, Mehra R, Khouri I et al. Chronic graft-versus-host disease after allogeneic blood stem cell transplantation. Blood 2001; 98: 1695–1700.

    Article  CAS  PubMed  Google Scholar 

  2. Cutler C, Giri S, Jeyapalan S, Paniagua D, Viswanathan A, Antin JH . Acute and chronic graft-versus-host disease after allogeneic peripheral-blood stem-cell and bone marrow transplantation: a meta-analysis. J Clin Oncol 2001; 19: 3685–3691.

    Article  CAS  PubMed  Google Scholar 

  3. Remberger M, Mattsson J, Hentschke P, Aschan J, Barkholt L, Svennilson J et al. The graft-versus-leukaemia effect in haematopoietic stem cell transplantation using unrelated donors. Bone Marrow Transplant 2002; 30: 761–768.

    Article  CAS  PubMed  Google Scholar 

  4. Mohty M, Kuentz M, Michallet M, Bourhis JH, Milpied N, Sutton L et al. Chronic graft-versus-host disease after allogeneic blood stem cell transplantation: long-term results of a randomized study. Blood 2002; 100: 3128–3134.

    Article  CAS  PubMed  Google Scholar 

  5. Miyakoshi S, Yuji K, Kami M, Kusumi E, Kishi Y, Kobayashi K et al. Successful engraftment after reduced-intensity umbilical cord blood transplantation for adult patients with advanced hematological diseases. Clin Cancer Res 2004; 10: 3586–3592.

    Article  PubMed  Google Scholar 

  6. Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, Miller JS, Wagner JE . Rapid and complete donor chimerism in adult recipients of unrelated donor umbilical cord blood transplantation after reduced-intensity conditioning. Blood 2003; 102: 1915–1919.

    Article  CAS  PubMed  Google Scholar 

  7. Sanz GF, Saavedra S, Planelles D, Senent L, Cervera J, Barragan E et al. Standardized, unrelated donor cord blood transplantation in adults with hematologic malignancies. Blood 2001; 98: 2332–2338.

    Article  CAS  PubMed  Google Scholar 

  8. Goggins TF, Rizzieri DR . Nonmyeloablative allogeneic stem cell transplantation using alternative donors. Cancer Control 2004; 11: 86–96.

    Article  PubMed  Google Scholar 

  9. Rocha V, Labopin M, Sanz G, Arcese W, Schwerdtfeger R, Bosi A et al. Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia. N Engl J Med 2004; 351: 2276–2285.

    Article  CAS  PubMed  Google Scholar 

  10. Laughlin MJ, Eapen M, Rubinstein P, Wagner JE, Zhang MJ, Champlin RE et al. Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med 2004; 351: 2265–2275.

    Article  CAS  PubMed  Google Scholar 

  11. Kurtzberg J, Laughlin M, Graham ML, Smith C, Olson JF, Halperin EC et al. Placental blood as a source of hematopoietic stem cells for transplantation into unrelated recipients. N Engl J Med 1996; 335: 157–166.

    Article  CAS  PubMed  Google Scholar 

  12. Rubinstein P, Carrier C, Scaradavou A, Kurtzberg J, Adamson J, Migliaccio AR et al. Outcomes among 562 recipients of placental-blood transplants from unrelated donors. N Engl J Med 1998; 339: 1565–1577.

    Article  CAS  PubMed  Google Scholar 

  13. Gluckman E, Rocha V, Boyer-Chammard A, Locatelli F, Arcese W, Pasquini R et al. Outcome of cord-blood transplantation from related and unrelated donors. Eurocord Transplant Group and the European Blood and Marrow Transplantation Group. N Engl J Med 1997; 337: 373–381.

    Article  CAS  PubMed  Google Scholar 

  14. Locatelli F, Rocha V, Chastang C, Arcese W, Michel G, Abecasis M et al. Factors associated with outcome after cord blood transplantation in children with acute leukemia. Eurocord-Cord Blood Transplant Group. Blood 1999; 93: 3662–3671.

    CAS  PubMed  Google Scholar 

  15. Rocha V, Wagner Jr JE, Sobocinski KA, Klein JP, Zhang MJ, Horowitz MM et al. Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical sibling. Eurocord and International Bone Marrow Transplant Registry Working Committee on Alternative Donor and Stem Cell Sources. N Engl J Med 2000; 342: 1846–1854.

    Article  CAS  PubMed  Google Scholar 

  16. Takahashi S, Iseki T, Ooi J, Tomonari A, Takasugi K, Shimohakamada Y et al. Single-institute comparative analysis of unrelated bone marrow transplantation and cord blood transplantation for adult patients with hematologic malignancies. Blood 2004; 104: 3813–3820.

    Article  CAS  PubMed  Google Scholar 

  17. Takahashi S, Ooi J, Tomonari A, Konuma T, Tsukada N, Oiwa-Monna M et al. Comparative single-institute analysis of cord blood transplantation from unrelated donors with bone marrow or peripheral blood stem-cell transplants from related donors in adult patients with hematologic malignancies after myeloablative conditioning regimen. Blood 2007; 109: 1322–1330.

    Article  CAS  PubMed  Google Scholar 

  18. Wagner JE, Barker JN, DeFor TE, Baker KS, Blazar BR, Eide C et al. Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival. Blood 2002; 100: 1611–1618.

    CAS  PubMed  Google Scholar 

  19. Michel G, Rocha V, Chevret S, Arcese W, Chan KW, Filipovich A et al. Unrelated cord blood transplantation for childhood acute myeloid leukemia: a Eurocord Group analysis. Blood 2003; 102: 4290–4297.

    Article  CAS  PubMed  Google Scholar 

  20. Thomson BG, Robertson KA, Gowan D, Heilman D, Broxmeyer HE, Emanuel D et al. Analysis of engraftment, graft-versus-host disease, and immune recovery following unrelated donor cord blood transplantation. Blood 2000; 96: 2703–2711.

    CAS  PubMed  Google Scholar 

  21. Narimatsu H, Terakura S, Matsuo K, Oba T, Uchida T, Iida H et al. Short-term methotrexate could reduce early immune reactions and improve outcomes in umbilical cord blood transplantation for adults. Bone Marrow Transplant 2007; 39: 31–39.

    Article  CAS  PubMed  Google Scholar 

  22. Akpek G, Zahurak ML, Piantadosi S, Margolis J, Doherty J, Davidson R et al. Development of a prognostic model for grading chronic graft-versus-host disease. Blood 2001; 97: 1219–1226.

    Article  CAS  PubMed  Google Scholar 

  23. Kim ST, Jung CW, Lee J, Kwon JM, Oh SY, Park BB et al. New clinical grading system for chronic GVHD predicts duration of systemic immunosuppressive treatment and GVHD-specific and overall survival. Bone Marrow Transplant 2007; 39: 711–716.

    Article  CAS  PubMed  Google Scholar 

  24. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant 2005; 11: 945–956.

    Article  PubMed  Google Scholar 

  25. Jacobsohn DA, Montross S, Anders V, Vogelsang GB . Clinical importance of confirming or excluding the diagnosis of chronic graft-versus-host disease. Bone Marrow Transplant 2001; 28: 1047–1051.

    Article  CAS  PubMed  Google Scholar 

  26. Jagasia M, Giglia J, Chinratanalab W, Dixon S, Chen H, Frangoul H et al. Incidence and outcome of chronic graft-versus-host disease using National Institutes of Health consensus criteria. Biol Blood Marrow Transplant 2007; 13: 1207–1215.

    Article  PubMed  Google Scholar 

  27. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transplant 1995; 15: 825–828.

    CAS  PubMed  Google Scholar 

  28. Sullivan KM, Agura E, Anasetti C, Appelbaum F, Badger C, Bearman S et al. Chronic graft-versus-host disease and other late complications of bone marrow transplantation. Semin Hematol 1991; 28: 250–259.

    CAS  PubMed  Google Scholar 

  29. Narimatsu H, Kami M, Miyakoshi S, Murashige N, Yuji K, Hamaki T et al. Graft failure following reduced-intensity cord blood transplantation for adult patients. Br J Haematol 2006; 132: 36–41.

    Article  PubMed  Google Scholar 

  30. Kishi Y, Kami M, Miyakoshi S, Kanda Y, Murashige N, Teshima T et al. Early immune reaction after reduced-intensity cord-blood transplantation for adult patients. Transplantation 2005; 80: 34–40.

    Article  PubMed  Google Scholar 

  31. Martin PJ, Schoch G, Fisher L, Byers V, Anasetti C, Appelbaum FR et al. A retrospective analysis of therapy for acute graft-versus-host disease: initial treatment. Blood 1990; 76: 1464–1472.

    CAS  PubMed  Google Scholar 

  32. Sullivan KM, Witherspoon RP, Storb R, Weiden P, Flournoy N, Dahlberg S et al. Prednisone and azathioprine compared with prednisone and placebo for treatment of chronic graft-v-host disease: prognostic influence of prolonged thrombocytopenia after allogeneic marrow transplantation. Blood 1988; 72: 546–554.

    CAS  PubMed  Google Scholar 

  33. Gooley TA, Leisenring W, Crowley J, Storer BE . Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 1999; 18: 695–706.

    Article  CAS  PubMed  Google Scholar 

  34. Coviello V, Boffess M . Cumulative incidence estimation in the presence of competing risks. Stata J 2004; 4: 103–112.

    Article  Google Scholar 

  35. Morishima Y, Sasazuki T, Inoko H, Juji T, Akaza T, Yamamoto K et al. The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A, HLA-B, and HLA-DR matched unrelated donors. Blood 2002; 99: 4200–4206.

    Article  CAS  PubMed  Google Scholar 

  36. Atsuta Y, Suzuki R, Yamamoto K, Terakura S, Iida H, Kohno A et al. Risk and prognostic factors for Japanese patients with chronic graft-versus-host disease after bone marrow transplantation. Bone Marrow Transplant 2006; 37: 289–296.

    Article  CAS  PubMed  Google Scholar 

  37. Sullivan KM, Witherspoon RP, Storb R, Deeg HJ, Dahlberg S, Sanders JE et al. Alternating-day cyclosporine and prednisone for treatment of high-risk chronic graft-v-host disease. Blood 1988; 72: 555–561.

    CAS  PubMed  Google Scholar 

  38. Siadak M, Sullivan KM . The management of chronic graft-versus-host disease. Blood Rev 1994; 8: 154–160.

    Article  CAS  PubMed  Google Scholar 

  39. Koc S, Leisenring W, Flowers ME, Anasetti C, Deeg HJ, Nash RA et al. Therapy for chronic graft-versus-host disease: a randomized trial comparing cyclosporine plus prednisone versus prednisone alone. Blood 2002; 100: 48–51.

    Article  CAS  PubMed  Google Scholar 

  40. Flowers ME, Parker PM, Johnston LJ, Matos AV, Storer B, Bensinger WI et al. Comparison of chronic graft-versus-host disease after transplantation of peripheral blood stem cells versus bone marrow in allogeneic recipients: long-term follow-up of a randomized trial. Blood 2002; 100: 415–419.

    Article  CAS  PubMed  Google Scholar 

  41. Subramaniam DS, Fowler DH, Pavletic SZ . Chronic graft-versus-host disease in the era of reduced-intensity conditioning. Leukemia 2007; 21: 853–859.

    Article  CAS  PubMed  Google Scholar 

  42. Chen BJ, Cui X, Sempowski GD, Gooding ME, Liu C, Haynes BF et al. A comparison of murine T-cell-depleted adult bone marrow and full-term fetal blood cells in hematopoietic engraftment and immune reconstitution. Blood 2002; 99: 364–371.

    Article  CAS  PubMed  Google Scholar 

  43. Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb HJ et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood 1990; 75: 555–562.

    CAS  PubMed  Google Scholar 

  44. Ringden O . Bone marrow transplantation using unrelated donors for haematological malignancies. Med Oncol 1997; 14: 11–22.

    Article  CAS  PubMed  Google Scholar 

  45. Sullivan KM . Graft-versus-host disease. In: Forman SJ (ed). Hematopoietic Cell Transplantation, 2nd edn. Blackwell: Boston, 1999, pp 515–536.

    Google Scholar 

  46. Ochs LA, Miller WJ, Filipovich AH, Haake RJ, McGlave PB, Blazar BR et al. Predictive factors for chronic graft-versus-host disease after histocompatible sibling donor bone marrow transplantation. Bone Marrow Transplant 1994; 13: 455–460.

    CAS  PubMed  Google Scholar 

  47. Zaucha JM, Gooley T, Bensinger WI, Heimfeld S, Chauncey TR, Zaucha R et al. CD34 cell dose in granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell grafts affects engraftment kinetics and development of extensive chronic graft-versus-host disease after human leukocyte antigen-identical sibling transplantation. Blood 2001; 98: 3221–3227.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Dr Yoshiko Atsuta (Nagoya University) for the critical reading of the manuscript. We also thank all the staff and resident members of the participating institutions. A complete list of participating institutions appears in the Appendix A.

Author information

Authors and Affiliations

  1. Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    K Sugimoto, H Narimatsu, S Terakura, T Naoe & M Murata

  2. Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan

    T Kawase & K Matsuo

  3. Department of Hematology, Meitetsu Hospital, Nagoya, Japan

    H Iida

  4. Department of Hematology, Fujita Health University Hospital, Toyoake, Japan

    M Watanabe

  5. Division of Hematology and Oncology, JA Aichi Showa Hospital, Konan, Japan

    A Kohno & Y Morishita

  6. Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    Y Kuwatsuka & K Miyamura

  7. Department of Hematology, Nagoya Daini Red Cross Hospital, Nagoya, Japan

    T Uchida

  8. Department of Hematology, Clinical and Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan

    M Hamaguchi

  9. Department of Hematology, Anjo Kosei Hospital, Anjo, Japan

    M Sawa

Authors
  1. K Sugimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H Narimatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T Kawase
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H Iida
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A Kohno
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Y Kuwatsuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. T Uchida
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. M Hamaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. S Terakura
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. T Naoe
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. K Matsuo
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. M Murata
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. M Sawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. K Miyamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Y Morishita
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

for the Nagoya Blood and Marrow Transplantation Group (NBMTG)

Corresponding author

Correspondence to H Narimatsu.

Appendix A

Appendix A

This study was conducted at the following NBMTG centers: Japanese Red Cross Nagoya First Hospital, Nagoya; Nagoya Daini Red Cross Hospital, Nagoya; Meitetsu Hospital, Nagoya; National Hospital Organization Nagoya Medical Center, Clinical and Research Center, Nagoya; Fujita Health University Hospital, Toyoake; JA Aichi Showa Hospital, Konan; Nagoya University Hospital, Nagoya and Anjo Kosei Hospital, Anjo, Japan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sugimoto, K., Narimatsu, H., Kawase, T. et al. Clinical characteristics of chronic graft-versus-host disease following umbilical cord blood transplantation for adults. Bone Marrow Transplant 41, 729–736 (2008). https://doi.org/10.1038/sj.bmt.1705959

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705959

Keywords

This article is cited by

Search

Advanced search

Quick links